Phamacokinetics 1 Flashcards
Define drug absorption
the process of transfer of a drug from the site of administration into the systemic circulation
What is the most common route of drug administration?
oral
How would you give diazepam for a fitting child - status epilepticus?
per rectum
how would you give a dye for an X-ray to look at the coronary arteries?
intra-arterial
How would you give an anti-emetic for a vomiting pt?
IV
How is insulin administered?
subcutaneous
Which route of administration is the exception to the rule that a drug must cross at least one membrane to get into the circulation
IV
What are the ways in which a drug can pass across a membrane?
passive diffusion through the lipid bilayer
diffusion through pores or ion channels
active transport - carrier mediated
facilitated diffusion - carrier mediated
pinocytosis
What factors determine the rate of passive diffusion?
conc gradient
thickness of membrane
SA and permeability of membrane
Which direction does diffusion through pores or ion channels occur - against or down the conc gradient?
down the conc gradient
What type of substance travels by diffusion through ion channels or pores?
very small water soluble molecules
Give an example of a drug that can diffuse through pores/ion channels and what was it used for?
lithium - for manic depression (bipolar)
What two processes come under carrier mediated transport?
active transport
facilitated diffusion
What does P-gp (multi-drug resistance MDR1) do?
it removes drugs from the cytoplasm to the extracellular side
Name one drug that interacts with P-gp and what this results in
Verapamil - increases the concentration of anti cancer drugs in the cytoplasm
What is pinocytosis?
A form of endocytosis usually involved in taking up surrounding fluids (and the substances this contains) into the cell
Why is drug ionisation needed?
ionic forces form part of the ligand receptor interaction
What does the extent of ionisation of a drug depend on?
strength of the ionisable group and the pH of the solution
What is the pKa of a drug?
the pH at which half of the substance is ionised and half is unionised
Where are weak acids best absorbed and why?
in the stomach, as weak acids are least ionised in acidic conditions
What is an acid?
A proton donor
Where are weak bases best absorbed?
in the intestine
How do we treat aspirin overdose?
administer IV bicarbonate to alkalinise urine, so faster elimination of aspirin
What are the advantages of oral administration?
easy
convenient
large SA of s. intestine
large blood supply of s.intestine so rapid adsorbtion
What factors affect oral absorption?
drug structure
drug formulation
gastric emptying
1st pass metabolism
How does drug structure influence oral adsorption?
lipid solubility - needs to be lipid soluble to be absorbed from the gut
polarisation - highly polarised drugs only partially absorbed and the rest goes into the faeces
instability at low pH or when there is digestive enzymes
How does drug formulation affect oral absorption?
modified release tablets dissolve slowly or have an enteric coating
what factors affect the rate of gastric emptying?
food
trauma
gastric surgery
What are the barriers that an oral drug has to go through to reach the systemic circulation?
intestinal lumen
intestinal wall
liver
What factors in the lumen hinder drug absorption?
digestive enzymes
colonic bacteria
What factors of the intestinal wall affect drug absorprion?
Monoamine oxidases are affected by foods
efflux transporters eg P-gp on enterocytes
short gut syndrome produced by extensive bowel surgery
Give an example of a drug that is taken up by pinocytosis?
Amphotericin (antifungal)
Which methods of drug administration avoid first pass?
per rectum IV sublingual intramuscular inhalation transdermal
Give an example of a drug which is given transcutaneously
Fentanyl
What are the disadvantages to transcutaneous?
limited rate and extent of absorption
what are the advantages of transcutaneous?
slow and continued absorption, good for drugs that need a long lasting effect
What are the advantages of intradermal and subcut?
avoids the stratum corneum
small volume can be given
local effect
can deliberately limit rate of absorption of drugs
What factor is intradermal and subcut absorption limited by?
blood flow
For what are depot injections used?
mental health
What are the advantages of the intranasal route?
low levels of proteases and drug metabolising enzymes
good SA
can be used for local or systemic effects
What are the a advantages of inhalational methods?
large SA
large blood flow
What are the limitations of inhalational methods
risk of toxicity to alveoli
difficult to deliver non-volatile drugs
What is the definition of distribution?
The process by which the drug is transferred reversibly from the general circulation to the tissues as the blood concentration increases and then returns from the tissues to the blood when the blood concentration falls
What two types of protein can drugs bind to?
plasma proteins
tissue proteins
Which protein is involved in the commonest type of protein binding?
albumin
Protein binding is always reversible? T or F
F - it can be irreversible eg some cytotoxic chemo drugs
Which types of drugs, lipid soluble or water soluble pass easier through the BBB?
lipid soluble drugs
Which drugs use the solute carreris that supply the brain with nutrients?
L-Dopa for parkinsons
How are drugs removed from the brain?
diffusion into the plasma
active transport into the choroid plexus
elimination in CSF
Which type of drugs, lipid or water soluble, cross the placenta easily?
lipid soluble drugs
What two processes are involved in elimination?
metabolism
excretion
What is metabolism of a drug?
the transformation of the drug molecule into a different molecule
What are the three states of excretion?
solid
liquid
gas
What are phase 1 reactions?
transformation of a drug into a more polar metabolite
done by unmasking or adding a functional group
oxidations are the commonest reaction
carried out mainly by CYP450 enzymes
Where are cyp450 enzymes present
in the smooth endoplasmic reticulum of the liver
What are phase 2 reactions?
conjugation - formation of a covalent bond between the drug/phase 1 metabolite an dan endogenous substrate eg glucoronic acid.
the resulting products are less active and readily excreted by the kidneys
What type of compounds are excreted in fluid form?
low molecular weight
polar
What type of compounds are excreted in solid form?
high MWT compounds
What type of compounds are excreted as gases?
volatile
what are the fluid forms of excretion?
urine , bile , sweat , tears , breast milk
What are the solid forms of excretion?
faeces and hair
What is the eqn for total excretion?
total excretion = glomerular filtration + tubular secretion - reabsorption
